American Journal of Transplantation 2009; 9 (Suppl 4): S267–S272
Wiley Periodicals Inc.
Urinary Tract Infections in Solid Organ Transplant
Recipients
J. C. Ricea,∗ , N. Safdarb and the AST Infectious
Diseases Community of Practice
a
Department of Nephrology, Center for Organ and Cell
Transplantation, Scripps Clinic and Scripps Green
Hospital, La Jolla, CA
b
Department of Medicine, Section of Infectious Diseases,
University of Wisconsin-Madison and Wm S Middleton
VA Center, Madison, WI
*Corresponding author: J. C. Rice, jrice@utmb.edu
Key words: Asymptomatic bacteriuria, candiduria,
cystitis, pyelonephritis, urinary tract infection,
uropathogen
Epidemiology and Risk Factors
Epidemiology
Urinary tract infection (UTI) is the most common infection
in the renal transplant patient, the majority occurring in
the first year following transplantation. Renal transplant
patients have higher rates of UTI, hospitalizations and
death due to Gram-negative septicemia associated with
pyelonephritis, compared with patients on the renal trans-
plant waiting list (1,2). Single center studies demonstrate
that acute pyelonephritis, especially early posttransplant
(3), represents a risk factor to long-term kidney graft func-
tion but does not affect graft survival at 5 years (4). Analysis
of the United States Renal Data System (USRDS) database
however, reveals that late UTI (>6 m after transplanta-
tion) is associated with poor renal allograft survival and
increased mortality (5). Confounding factors that may con-
tribute to renal allograft injury during UTI in the renal trans-
plant patient include the combined effects of calcineurin-
inhibitors with endotoxin (6,7), rejection (8) and recurrent
UTI (5,9).
Escherichia coli is the most common uropathogen among
renal transplant patients, accounting for the majority of
bacteriuria and UTI episodes with Enterococcus species,
Pseudomonas, coagulase-negative staphylococci, Enter-
obacter and other organisms (group B streptococci, and
Gardnerella vaginalis) also occurring (Figure 1) (4,10–14).
Corynebacterium urealyticum is an emerging pathogen
that requires selective media, is frequently associated
C 2009 The Authors
Journal compilation 
C 2009 The American Society of
Transplantation and the American Society of Transplant Surgeons
doi: 10.1111/j.1600-6143.2009.02919.x
with obstructive uropathy, and is a potentially important
uropathogen as it is not susceptible to most conventional
oral antibiotics used for treatment of UTI (15).
Virulence factors, like P. fimbriae, are expressed on the
surface of uropathogenic bacteria and facilitate adhesion
to uroepithelial surface. E. coli that express P fimbriae ac-
count for more than 80% of the isolates from patients
with pyelonephritis in the noncompromised host (16) and
the majority of pyelonephritis isolates from immunosup-
pressed patients (17,18). In addition, a subset of O antigen
serotypes are present on the majority (80%) of E. coli iso-
lates from patients with UTI (11,19). Although most studies
document a decreased prevalence of virulence factors ex-
pressed by uropathogenic E. coli from compromised hosts,
likely reflecting the weaker barriers to infection in this pop-
ulation (17), a recent report suggests that unique patterns
of uropathogenic of O:H serotypes and P fimbriae adher-
ence factor among E. coli isolates from renal transplant
patients with UTI (20).
Risk factors
The most frequently reported patient and graft character-
istics associated with susceptibility to UTI in the renal
transplant patients include female gender (4), recipients
of cadaveric kidneys (13), recipients of kidney–pancreas
transplants (5), prolonged bladder catheterization (21) or
uretero-vesical stenting (22) and overall net state of im-
munosuppression (23) (Table 1). Whether specific immuno-
suppressive agents are more likely to encourage UTI is un-
clear, although mycophenolic acid may predispose to UTI
and pyelonephritis (24,25). Vesico-ureteral reflux (VUR) is
common in the renal transplant recipient and children with
VUR have an increased risk of acute pyelonephritis (26)
and allograft scarring (27). In adults, UTI is not more com-
mon in patients with VUR (28). However, adult renal trans-
plant patients with late UTI and VUR are prone to allograft
scarring (29).
Candiduria
Candida species are among the most common fungal
causes of UTI in persons who have undergone renal
transplantation. While candiduria is frequent, occurring in
11% of renal transplant patients in one series (30), it is
most often asymptomatic. Although most risk factors for
candiduria are similar to those predisposing to bacterial
UTI, important differences include the close association of
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Rice et al.

Figure 1: Microbiology of urinary

tract infections in renal transplant
recipients. Proportion of isolates in
each category (N = 1519 isolates). Data
taken from Chuang (13), Memikoglu
(14), Pelle (4) and DiCocco (56).

candiduria with prior antibiotic use and severe illness re- Diagnosis
quiring ICU care.
The diagnosis of a symptomatic UTI requires a quantita-
UTI in the nonrenal transplant recipient tive count of bacteria (≥105 ) in an appropriately collected
The incidence of UTI in immunosuppressed patients, in- urine specimen in the presence of symptoms or signs of
cluding solid organ transplants other than renal transplant urinary infection (34). However, the RTP may not present
patients, is not higher than nonimmunosuppressed indi- with classic symptoms of UTI and the lack of symptoms
viduals (31). The addition of a pancreas transplant to a kid- is an important distinguishing feature of UTI in the renal
ney transplant is associated with frequent UTIs, especially allograft recipient (35). The majority of renal transplant re-
when exocrine secretions are drained into the bladder. The cipients with bacteriuria do not have symptoms with their
frequency of UTIs are significantly less when exocrine pan- UTI, hence have ’asymptomatic bacteriuria’ (ASB) (36,37).
creas secretions are drained enterically (32,33). Renal transplant patients with ASB have biochemical evi-
dence of local inflammation, as urinary cytokine levels are
higher than in transplant patients without bacteriuria and
are more likely to develop symptomatic UTI within the next
Table 1: Major risk factors for bacterial urinary tract infection, year (38). ‘Acute cystitis’ is a symptomatic infection of the
candiduria and pyelonephritis in renal transplant recipients
lower bladder with frequency, urgency, dysuria or supra-
Risk factor (references) OR (95% CI) pubic pain sometimes accompanied by low-grade fever
Bacterial urinary tract infection (13,24,54,57) <38.3◦ C, but without flank pain or renal allograft tender-
Female gender 5.8 (3.79–8.89) ness. ‘Acute pyelonephritis’ is an infection of the upper
Age (per year) 0.02 (1.01–1.04) urinary tract or renal parenchyma, characterized by cos-
Reflux kidney disease prior to 3.0 (1.05–8.31) tovertebral angle pain (if native kidneys involved) or renal
transplantation allograft tenderness (if transplanted kidney involved) often
Deceased donor 3.64 (1.0–12.7) with fever ≥ 38.3◦ C. ‘Complicated UTI’ is an infection in in-
Duration of bladder catheterization 1.50 (1.1–1.9) \
dividuals with functional or structural abnormalities of the
Length of hospitalization prior to UTI 0.92 (0.88–0.96)
Increase in immunosuppression 17.04 (4.0–71.5)
genitourinary tract and that may involve either the blad-
Candiduria (30) der or kidneys (39). Hence, all UTIs in the renal transplant
Female gender 12.5 (6.70–23.0) patient should be considered complicated UTIs, due to
ICU care 8.8 (2.3–35.0) functional (immunosuppression) and structural abnormal-
Prior antibiotic use 3.8 (1.7–8.3) ities (resulting from uretero-neocystostomy).
Indwelling urethral catheter 4.4 (2.1–9.4)
Neurogenic bladder 7.6 (2.1–27)
Malnutrition 2.4 (1.3–4.4)
Acute pyelonephritis (4,25) Treatment
Female gender 5.14 (1.86–14.20)
Acute rejection episodes 3.84 (1.37–10.79) Antibiotic resistance of uropathogens
Number of UTIs 1.17 (1.06–1.30) The prevalence of resistance to other antibiotics among
Mycophenolate mofetil 1.9 (1.2–2.3)
uropathogenic bacteria is increasing (40–42), resulting in
NR, not reported. the rapid emergence of multidrug resistant strains and

S268 American Journal of Transplantation 2009; 9 (Suppl 4): S267–S272


a higher incidence of treatment failure and re-infection
(43). The prevalence of drug resistance varies consider-
ably by region and country, thus, awareness of local and
regional antibiotic susceptibility among uropathogens is
recommended to optimize empiric treatment. While the
general principles of antibiotic treatment of asymptomatic
bacteriuria, cystitis and acute pyelonephritis are similar in
transplant and nontransplant patients, several important
distinctions deserve mention (44,45).
Asymptomatic bacteriuria
There is not a consensus whether ASB, the isolation of bac-
teria (≥105 ) in an appropriately collected urine specimen
in the absence of symptoms or signs of urinary infection,
should be treated in the transplant patient and if so, at what
time points posttransplant (37). A prospective randomized
trial does suggest that treatment of ASB beyond one year
does not prevent symptomatic UTI (46).
Cystitis
Historically, prolonged therapy for early UTI infections
(within the first 3 months of transplant) was recommended
because of the risk of pyelonephritis, bacteremia and graft
loss based on noncomparative studies (47). However, with
advancement in surgical techniques and the availability
of more potent effective antimicrobials in recent years,
prolonged therapy is not considered necessary for first
episodes of UTI.
Acute pyelonephritis
A Gram stain of a urine specimen should be performed to
guide therapy. An oral fluoroquinolone may be used empir-
ically. If there is evidence of Gram-positive cocci on Gram
stain, coverage for enterococcus with amoxicillin should
be added until the causative organism is identified. For
patients that require initial parenteral therapy because of
severe illness or nausea and vomiting, beta-lactams such
as ceftriaxone or a fluoroquinolone may be used. The du-
ration of therapy has not been specifically studied in trans-
plant patients. In nontransplant patients, a 7–14 day course
is recommended; a short course (3-day) treatment of UTI
has not been studied in transplant patients and is not rec-
ommended. Imaging of the genitourinary tract should be
undertaken in transplant patients who continue to have per-
sistent symptoms despite appropriate therapy to evaluate
for complicated pyelonephritis.
Complicated pyelonephritis
Progression of upper urinary tract disease, to a nephric
or perinephric abscess or emphysematous pyelonephritis
may occur and usually requires a multidisciplinary approach
to treatment, including urologic and/or interventional radiol-
ogy consultation for percutaneous or surgical drainage of
abscesses. Broad-spectrum anti-infective therapy should
be initiated, with a carbapenem, extended spectrum peni-
cillin, or third generation cephalosporin. Duration of treat-
American Journal of Transplantation 2009; 9 (Suppl 4): S267–S272
UTI in Transplant Patients
ment should be at least 2 weeks and should be extended
until adequate drainage of abscesses has been achieved.
Relapsing UTI
Anatomic abnormalities must be excluded in renal trans-
plant patients with a relapsing UTI. In the face of a re-
lapsing UTI in a renal transplant recipient, the most com-
mon findings include vesico-ureteral reflux, strictures at
the ureterovesical junction and neurogenic bladder (45).
Candiduria
Further research is necessary to determine whether
asymptomatic candiduria warrants treatment in renal trans-
plant patients, as data on treatment of candiduria in renal
transplantation is scant. In one observational case control
study of 192 renal transplant recipients with candiduria,
50% were not treated with antifungal therapy. Treatment
of asymptomatic candiduria was not associated with im-
proved clinical outcomes (30). Many asymptomatic pa-
tients with candiduria are treated because of the perceived
risk to the allograft and the potential for involvement of
the upper urinary tract. Hence, recent guidelines from the
Infectious Diseases Society of America recommend treat-
ment of candiduria in patients with renal allografts, prefer-
ably with fluconazole, 200 mg orally per day for 7–14 days
or intravenous amphotericin B, 0.3–1 mg/kg/day for 1–7
days; bladder irrigation with amphotericin B is of limited
value (48). The echinocandins achieve low concentrations
in the urinary tract, which precludes their use for treatment
of fungal urinary tract infection. Removal (preferred) or re-
placement of urinary tract instruments such as urologic
stents and urethral catheters is recommended.
Prevention and Prophylaxis
Prevention of both ASB and UTI posttransplant improved
with the introduction of routine perioperative antibiotic
prophylaxis, minimization of use of indwelling urethral
catheters and long-term use of antimicrobial prophylaxis
to prevent pneumonia and other infections (21,49). Studies
published more than 15 years ago demonstrated that pro-
phylaxis with trimethoprim-sulfamethoxazole (TMP-SMX)
reduced the risk of UTI three-fold, did not result in sig-
nificant colonization by TMP-SMZ resistant Gram-negative
bacilli (49,50), and led to recommendations for use of
prophylactic antibiotics (TMP-SMX) for 6 months–1 year
posttransplant (45). As uropathogenic bacteria have be-
come more TMP-SMX resistant (40,41), prophylaxis with
TMP-SMX may be less effective for the prevention of
UTI in transplant recipients. Although antibiotic prophy-
laxis remains the standard-of-care in most renal trans-
plant programs (51), no recent guidelines address the
optimal drug, dose or duration of antibiotic prophylaxis or
antibiotic susceptibility of UTI isolates in the posttransplant
population (52).
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Rice et al.
As earlier reports did not demonstrate a clear associa-
tion between UTI and impaired renal allograft survival, un-
less the UTI occurred within 3 months after transplanta-
tion (3) or was associated with a urological complication
(53), screening for UTI has been recommended for renal
transplant recipients only in the early months (<6 m) post-
transplant. Recent guidelines from the Infectious Disease
Society of American acknowledge that at present, ‘no rec-
ommendations can be made for screening for or treatment
of ASB in renal transplant or other solid organ transplant
recipients’ (37).
Future studies are needed to determine: (1) the clini-
cal consequences and appropriate treatment strategy for
ASB in the renal and nonrenal transplant recipient, (2) the
prevalence of antibiotic-resistant uropathogens in the renal
transplant population (3) if the increased antibiotic resis-
tance of uropathogenic bacteria contributes to increased
infection rates and potentially, limits long-term renal allo-
graft function and (4) whether symptomatic candiduria war-
rants treatment in transplant patients.
Infection Control Issues
The increase in resistance to antiinfectives noted among
uropathogens in renal transplant patients has important
implications for healthcare institutions. Nosocomial cross-
transmission of resistant Gram-negative pathogens has
been reported (54). Healthcare workers should use con-
tact isolation precautions for patients, known to be col-
onized with resistant organisms. It is unknown whether
microbiologic surveillance for the presence of resistant
uropathogens is beneficial in preventing transmission. Lim-
iting the duration of urinary tract instrumention to the min-
imum necessary reduces the risk of UTI in the renal trans-
plant patient (49).
Specific recommendations:
(1) Limit duration of urinary tract instrumentation, includ-
ing catheters and uretero-vesicle stents, in renal trans-
plant patients. [I] (21,22)
(2) Antibiotic prophylaxis is recommended during the first
3–6 months posttransplant with either TMP-SMX or
ciprofloxacin, despite high levels of antibiotic resis-
tance to TMP-SMX. [I] (49,50,55)
(3) Urine cultures are needed to confirm infection, identify
the bacterial strain and determine antibiotic sensitivity,
due to high levels of antibiotic resistance of urinary
isolates in the transplant population. [I] (41)
(4) No recommendations can be made about diagnosis or
treatment of asymptomatic bacteriuria or candiduria in
the renal allograft recipient. [II] (37)
(5) Any UTI in a renal transplant patient should be con-
sidered a complicated UTI and diagnosis and manage-
ment should be undertaken with these factors under
consideration. [III].
S270 American Journal of Transplantation 2009; 9 (Suppl 4): S267–S272
(6) There are no data to support short-term treatment of
UTI in the transplant patient, hence short-term treat-
ment is not recommended. [III]
Disclosure
The authors have nothing to disclose.
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